Abstract: Melanoma Program (MP) The overall mission of the Melanoma Program (MP) is to improve the clinical outcome of patients with melanoma. MP members conduct basic and translational research studies to elucidate the mechanisms of melanoma progression, and the critical pathways of melanoma immune escape, to translate laboratory findings into novel therapies for both advanced and adjuvant disease settings. Research within the MP falls under three central themes: 1) immunology and immunotherapy of melanoma; 2) investigation and treatment of melanoma brain metastasis; and 3) novel investigator-initiated trials (IITs) and combinations for adjuvant and neo- adjuvant interventions for resectable disease as well as for the early detection and prevention of melanoma. Specific aims of the MP are to: 1) understand the basic tumor and immune mechanisms of progression and resistance to therapy; 2) identify new biomarkers of clinical outcome in patients treated in the adjuvant, neoadjuvant, and advanced disease settings; and 3) translate laboratory findings into novel IITs with correlative studies at UPCI and in the cooperative groups. The Program has 13 members representing 6 departments in 2 schools at the University of Pittsburgh. The MP is supported by NIH/NCI extramural grants including an NCI Specialized Program of Research Excellence (SPORE) in Melanoma and Skin Cancer. MP members currently receive a total of $4.2 M in annual direct funding, of which nearly all peer-reviewed support is provided by the NCI ($1.8 M). Between January 2010 and April 2014, MP members published 190 cancer- related publications, of which 38% resulted from intra-programmatic and 46% from inter-programmatic collaborations. Approximately 41% of the papers represent collaborations with external investigators. Collaborative efforts are fostered by weekly translational research meetings that review all active and pending MP clinical trials, as well as weekly clinical pathology reviews and monthly research seminars that bring members from multiple other UPCI programs together for interdisciplinary scientific discussion. The phase II and III studies of the ECOG-ACRIN Cooperative Group have emerged in part from the work of the MP, whose members are actively engaged in the research agenda of the National Cooperative Groups, and serve as lead investigators or co-investigators on ECOG-ACRIN and Intergroup initiatives. UPCI support, including Clinical Protocol and Data Management and Shared Resources, specifically the Biostatistics Facility, Cancer Bioinformatics Services, Cancer Genomics Facility, Cancer Pharmacokinetics and Pharmacodynamics Facility, Cancer Proteomics Facility, Cell and Tissue Imaging Facility, Cytometry Facility, Immunological Monitoring and Cellular Products Laboratory, In Vivo Imaging Facility, Investigational Drug Services, and Tissue and Research Pathology Services facilitates and enhances MP research.